Small Molecule Modulators of β-arrestins.

Unlabelled: β-arrestins (βarrs) are key regulators of G protein-coupled receptors (GPCRs), essential for modulating signaling pathways and physiological processes. While current pharmacological strategies target GPCR orthosteric and allosteric sites, as well as G protein transducers, comparable tools for studying βarrs are lacking. Here, we present the discovery and characterization of novel small-molecule allosteric inhibitors of βarrs through comprehensive biophysical, biochemical, pharmacological, and structural analyses.

Risk and Reward: Nationwide Analysis of Cardiac Transplant Center Variation in Organ Travel Distance and the Effects on Outcomes.

Background: The 2018 UNOS allocation policy change deprioritized geographic boundaries to organ distribution, and the effects of this change have been widespread. The aim of this investigation was to analyze changes in donor transplant center distance for organ travel and corresponding outcomes before and after the allocation policy change.

Methods: The UNOS database was utilized to identify all adult patients waitlisted for heart transplants from 2016 to 2021.

Top Ten Tips Palliative Care Clinicians Should Know About Caring for Patients with Myeloproliferative Neoplasms.

Myeloproliferative neoplasms (MPNs) are a group of rare chronic progressive blood cancers that vary widely in clinical presentation, yet all patients have a risk of disease progression and thrombotic complications. Diseases include primary myelofibrosis, polycythemia vera, and essential thrombocythemia. With current treatment approaches, most patients live a prolonged life, but many experience a complex of symptoms that negatively influence their functional status and quality of life.

NCCN Guidelines® Insights: Systemic Mastocytosis, Version 3.2024.

Mastocytosis is a heterogeneous group of disorders comprising cutaneous mastocytosis, systemic mastocytosis, and mast cell sarcoma. It is associated with a variety of symptoms related to the release of mast cell mediators and mast cell tissue infiltration. Referral to specialized centers with expertise in the management of mastocytosis and multidisciplinary collaboration with subspecialists (eg, allergists for the management of anaphylaxis and drug hypersensitivities, anesthesiologists for invasive procedures or surgery, high-risk obstetrician for pregnancy) is recommended.

A Retrospective Cohort Analysis of Analgosedation Requirements in COVID-19 Compared to Non-COVID-19 Extracorporeal Membrane Oxygenation Patients.

Background: Reports have described increased sedation requirements in patients with acute respiratory distress syndrome (ARDS) while on extracorporeal membrane oxygenation (ECMO) and for intubated COVID-19 patients. Thus, the objective of this study was to assess the analgosedation requirements of COVID-19 patients receiving ECMO compared to non-COVID-19 ECMO patients.

Methods: This retrospective, observational cohort study included adult patients with ARDS requiring venovenous or venopulmonary arterial ECMO admitted to a single intensive care unit from January 2017 to December 2021.